Intraprostatic Chronic Inflammation is Associated with a Reduced Risk of Prostate Cancer in Patients Elected to a First Random Biopsy Set

Abstract

Objectives

To investigate the associations of clinical factors and intraprostatic chronic inflammatory infiltrate (CII) with the risk of prostate cancer (PCa) in a large contemporary cohort of patients elected to a first random biopsy set.

Materials and Methods

The study evaluated 596 patients who were elected to a first random biopsy set because of suspected PCa in the period between September 2010 and September 2015. The multivariate logistic regression model investigated the possible associations of clinical factors and intraprostatic CII with PCa.

Results

Prostate cancer was detected in 292 of 596 patients (49%). Intraprostatic CII was detected in 26.3% of cases. Age (odds ratio, OR = 1.060; p<.0001), prostate-specific antigen (PSA; OR = 1.174; p<.0001), prostate volume (PV; OR = 0.951; p<.0001) and abnormal digital rectal examination (DRE; OR = 2.170; p = 0.001) were independent predictors of PCa risk; moreover, intraprostatic CII was an important independent factor lowering the risk of PCa (OR = 0.258; p<.0001) in the multivariate clinical model.

Conclusions

In a large contemporary cohort of patients elected to a first random biopsy set, the detection of intraprostatic CII was not negligible (26.3%) and associated with a reduced risk of PCa. In the prostate microenvironment, intraprostatic CII might lower the risk of PCa by activating the response of the immune system at the early stages of cancer induction and progression. Specific serum biomarkers and imaging modalities associated with intraprostatic CII are required. Advanced basic science research is warranted to investigate and develop the controversial topic of intraprostatic chronic inflammation in relation to PCa.

Keywords

Chronic prostate inflammation Prostate biopsy Prostate cancer Prostate-specific antigen Prostate volume

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References

Balkwill

Mantovani

Inflammation and cancer: back to Virchow?

Lancet. 2001;357 (9255):539–545.

Coussens

Werb

Inflammation and cancer. Nature. 2002;420 (6917):860–867.

Kuraishy

Karin

Grivennikov

Tumor promotion via injury- and death-induced inflammation. Immunity. 2011;35 (4):467–477.

Mantovani

Allavena

Sica

Balkwill

Cancer-related inflammation. Nature. 2008;454 (7203):436–444.

Selman

The McNeal prostate: a review. Urology. 2011;78 (6):1224–1228.

Gandaglia

Briganti

Gontero

The role of chronic prostatic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH). BJU Int. 2013;112 (4):432–441.

De Nunzio

Kramer

Marberger

The controversial relationship between benign prostatic hyperplasia and prostate cancer: the role of inflammation. Eur Urol. 2011;60 (1):106–117.

Krieger

Nyberg

Jr Nickel

NIH consensus definition and classification of prostatitis. JAMA. 1999;282 (3):236–237.

Porcaro

Rubilotta

Petrozziello

Chronic inflammation of the prostate type IV with respect to risk of prostate cancer. Arch Ital Urol Androl. 2014;86 (3):208–211.

10.

Porcaro

Novella

Molinari

Prostate volume index and chronic inflammation of the prostate type IV with respect to the risk of prostate cancer. Urol Int. 2015;94 (3):270–285.

11.

Blumenfeld

Tucci

Narayan

Incidental lymphocytic prostatitis. Selective involvement with nonmalignant glands. Am J Surg Pathol. 1992;16 (10):975–981.

12.

Zhang

Sesterhenn

Connelly

Mostofi

Moul

Inflammatory infiltrate (prostatitis) in whole mounted radical prostatectomy specimens from black and white patients is not an etiology for racial difference in prostate specific antigen. J Urol. 2000;163 (1):131–136.

13.

Gerstenbluth

Seftel

MacLennan

Distribution of chronic prostatitis in radical prostatectomy specimens with up-regulation of bcl-2 in areas of inflammation. J Urol. 2002;167 (5):2267–2270.

14.

Irani

Goujon

Ragni

et al; Pathologist Multi Center Study Group. High-grade inflammation in prostate cancer as a prognostic factor for biochemical recurrence after radical prostatectomy. Urology. 1999;54 (3):467–472.

15.

Karakiewicz

Benayoun

Bégin

Chronic inflammation is negatively associated with prostate cancer and high-grade prostatic intraepithelial neoplasia on needle biopsy. Int J Clin Pract. 2007;61 (3):425–430.

16.

Moreira

Nickel

Gerber

Baseline prostate inflammation is associated with a reduced risk of prostate cancer in men undergoing repeat prostate biopsy: results from the REDUCE study. Cancer. 2014;120 (2):190–196.

17.

Moreira

Nickel

Andriole

Castro-Santamaria

Freedland

Chronic baseline prostate inflammation is associated with lower tumour volume in men with prostate cancer on repeat biopsy: results from the REDUCE study. Prostate. 2015;75 (13):1492–1498.

18.

Roberts

Bergstralh

Bass

Lieber

Jacobsen

Prostatitis as a risk factor for prostate cancer. Epidemiology. 2004;15 (1):93–99.

19.

Davidsson

Fiorentino

Andrén

Inflammation, focal atrophic lesions, and prostatic intraepithelial neoplasia with respect to risk of lethal prostate cancer. Cancer Epidemiol Biomarkers Prev. 2011;20 (10):2280–2287.

20.

Engelhardt

Brustmann

Seklehner

Riedl

Chronic asymptomatic inflammation of the prostate type IV and carcinoma of the prostate: is there a correlation?

Scand J Urol. 2013;47 (3):230–235.

21.

Porcaro

Novella

Balzarro

Prostate chronic inflammation type IV and prostate cancer risk in patients undergoing first biopsy set: results of a large cohort study. Asian Journal of Urology. 2015;2 (4):224–232.

22.

Porcaro

Novella

Mattevi

Chronic inflammation in prostate biopsy cores is an independent factor that lowers the risk of prostate cancer detection and is inversely associated with the number of positive cores in patients elected to a first biopsy. Curr Urol. 2016;9 (2):82–92.

23.

Epstein

Allsbrook

Jr Amin

Egevad

ISUP Grading Committee. The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma. Am J Surg Pathol. 2005;29 (9):1228–1242.

24.

Pierorazio

Walsh

Partin

Epstein

Prognostic Gleason grade grouping: data based on the modified Gleason scoring system. BJU Int. 2013;111 (5):753–760.

25.

Epstein

Zelefsky

Sjoberg

A contemporary prostate cancer grading system: a validated alternative to the Gleason score. Eur Urol. 2016;69 (3):428–435.

26.

Roobol

Schröder

Hugosson

Importance of prostate volume in the European Randomised Study of Screening for Prostate Cancer (ERSPC) risk calculators: results from the prostate biopsy collaborative group. World J Urol. 2012;30 (2):149–155.

27.

Al-Azab

Toi

Lockwood

Kulkarni

Fleshner

Prostate volume is strongest predictor of cancer diagnosis at transrectal ultrasound-guided prostate biopsy with prostate-specific antigen values between 2.0 and 9.0 ng/mL. Urology. 2007;69 (1):103–107.

28.

Sfanos

Hempel

De Marzo

The role of inflammation in prostate cancer. Adv Exp Med Biol. 2014;816:153–181.

29.

De Marzo

Platz

Sutcliffe

Inflammation in prostate carcinogenesis. Nat Rev Cancer. 2007;7 (4):256–269.

30.

Sfanos

De Marzo

Prostate cancer and inflammation: the evidence. Histopathology. 2012;60 (1):199–215.

31.

Strasner

Karin

Immune infiltration and prostate cancer. Front Oncol. 2015;5:128.

32.

Thun

Henley

Patrono

Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues. J Natl Cancer Inst. 2002;94 (4):252–266.

33.

Jacobs

Rodriguez

Mondul

A large cohort study of aspirin and other nonsteroidal anti-inflammatory drugs and prostate cancer incidence. J Natl Cancer Inst. 2005;97 (13):975–980.

34.

Pruthi

Derksen

Moore

A pilot study of use of the cyclooxygenase-2 inhibitor celecoxib in recurrent prostate cancer after definitive radiation therapy or radical prostatectomy. BJU Int. 2004;93 (3):275–278.

35.

Di Silverio

Sciarra

Gentile

Etoricoxib and intermittent androgen deprivation therapy in patients with biochemical progression after radical prostatectomy. Urology. 2008;71 (5):947–951.

36.

Bardia

Platz

Yegnasubramanian

De Marzo

Nelson

Anti-inflammatory drugs, antioxidants, and prostate cancer prevention. Curr Opin Pharmacol. 2009;9 (4):419–426.

37.

Gridley

McLaughlin

Ekbom

Incidence of cancer among patients with rheumatoid arthritis. J Natl Cancer Inst. 1993;85 (4):307–311.

38.

Langman

Cheng

Gilman

Lancashire

Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database. BMJ. 2000;320 (7250):1642–1646.

39.

Neugut

Rosenberg

Ahsan

Association between coronary heart disease and cancers of the breast, prostate, and colon. Cancer Epidemiol Biomarkers Prev. 1998;7 (10): 869–873.

40.

Drake

Prostate cancer as a model for tumour immunotherapy. Nat Rev Immunol. 2010;10 (8):580–593.

41.

Hammerstrom

Cauley

Atkinson

Sharma

Cancer immunotherapy: sipuleucel-T and beyond. Pharmacotherapy. 2011;31 (8):813–828.

42.

Hoekx

Jeuris

Van Marck

Wyndaele

Elevated serum prostate specific antigen (PSA) related to asymptomatic prostatic inflammation. Acta Urol Belg. 1998;66 (3):1–2.

43.

Sindhwani

Wilson

Prostatitis and serum prostate-specific antigen. Curr Urol Rep. 2005;6 (4):307–312.

44.

Hochreiter

The issue of prostate cancer evaluation in men with elevated prostate-specific antigen and chronic prostatitis. Andrologia. 2008;40 (2):130–133.

45.

Mendhiratta

Meng

Taneja

Using multiparametric MRI to ‘personalize’ biopsy for men. Curr Opin Urol. 2015;25 (6):498–503.